China
Africa
Explore chapters and articles related to this topic
Chemopreventive Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Interestingly, the SNAIL signaling pathway triggers breast cancer metastasis but has no relevance in pancreatic cancer models. Also, EMT can be reversed via Mesenchymal-Epithelial Transition (MET) which is thought to facilitate the implanting of circulating tumor cells to develop secondary tumors when they reach a desirable target metastatic site. As part of this processes, the Extracellular Matrix (ECM) must be degraded, which is carried out by a proteolytic enzyme family, the Matrix Metalloproteinases (MMPs). These enzymes are key to tumor invasion, allowing tumor cells to degrade the ECM, penetrate the basement membrane, and move to other sites. MMPs also regulate cellular adhesion, which makes it easier for tumor cells to migrate. Cell Adhesion Molecules (CAMs) also play a significant role in tumor development and metastases, and include four groups: the Cadherins, Selectins, Integrins, and the Immunoglobulin Superfamily. A reduction or loss in Cadherin expression has been observed in some epithelial cancers, which is associated with increased invasion and metastasis. Activation of CAM proteins, including kinases and chemokines, can induce downstream signaling pathways, which ultimately promotes tumor growth and progression. Some chemopreventive agents are thought to work by inhibiting key regulators to suppress tumor invasion and metastasis.
Cell Components and Function
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Most cells except for red blood cells have integral membrane proteins that attach to the extracellular matrix or with adhesion molecules on neighbouring cells. These molecules hold the tissue together and permit the transmission of mechanical forces from one cell to another. Some also act as receptors. The integrins are cell-matrix adhesion molecules that link cells to fibronectin or laminin in the extracellular matrix. The cadherins are glycoproteins that mediate Ca-dependent cell–cell adhesion. They bind to a copy of the molecule to cadherins on the other molecule. Intercellular adhesion molecules (ICAMS) are expressed on capillary endothelial cell surfaces that are activated by infection of surrounding tissue. They bind to integrins on white cells and promote their movement to sites of infection. Selectins are carbohydrate binding proteins on endothelial cell membranes that recognize sugars on white blood cell surfaces and form the initial binding, which is strengthened by ICAMs.
Epithelial Cells
Published in Bruce S. Bochner, Adhesion Molecules in Allergic Disease, 2020
The cadherins are a group of calcium-dependent cell-surface adhesion molecules that mediate cell–cell adhesion. They are made up of a single polypeptide chain and engage in homophilic adhesion of one cadherin molecule to another on an opposing cell membrane (60). Epithelial cadherin (E-cadherin, also called uvomorulin, Arc-1, liver cell adhesion molecule, L-CAM, and cell CAM 120/80) has been identified as a constituent of intermediate junctions in the bronchial epithelium. It localizes by immunofluorescence to the lateral cell membrane close to the luminal surface (45). Recent determination of the solution structure of E-cadherin revealed unexpected structural similarities to the immunoglobulin fold. The molecule has seven β-strands arranged in a “β-barrer topology, and two short α-helices, one of which provides the calcium-binding pocket. The putative adhesion interface is centered around the F-strand of the β-sheet and contains a conserved His-Ala-Val sequence (81). E-cadherin has been implicated in the suppression of tumor invasiveness, as its expression is decreased in the invasive phase of epithelial malignancies (82–84).
Dual role of E-cadherin in cancer cells
Published in Tissue Barriers, 2022
Svetlana N. Rubtsova, Irina Y. Zhitnyak, Natalya A. Gloushankova
E-cadherin, long known for its tumor suppressing role, has been revealed to be a “double agent”, equally adept at tumor promotion. Many carcinomas retain E-cadherin expression during their progression, owing to its assisting tumor cell survival and enhancing their invasive and metastatic potential. Replacement of E-cadherin-based stable linear AJs with dynamic punctate AJs and formation of cadherin AJs with adjacent normal cells enhance invasive and metastatic properties of cancer cells. Collective invasion and dissemination by CTC clusters, supported by E-cadherin, are among the crucial negative prognostic factors. N- and P- cadherins expressed de novo in various carcinomas via “cadherin switching” are also associated with an increase in invasion and metastasis. Cancer cells are able to harness the broad scope of AJ protein functions, not at all limited by promoting stable cell–cell adhesion, and use it to their advantage. Further research is required, however, to elucidate the precise molecular mechanisms of the tumor promoting function of cadherins.
Cell-cell junctions: structure and regulation in physiology and pathology
Published in Tissue Barriers, 2021
Mir S. Adil, S. Priya Narayanan, Payaningal R. Somanath
AJs are primarily made up of cadherin–catenin protein complexes, which are linked to the actin cytoskeleton.40 While cadherins make the transmembrane protein part, plaque proteins are made up of catenins, plakoglobin, p120, and others.31 Over 170 proteins have been reported to colocalize with cadherin or catenins in AJs, and either directly interact with them or affect AJ dynamics.41 Cadherins are transmembrane, calcium-dependent membrane proteins8,41–43 that have an ectodomain consisting of five cadherin motifs and a cytoplasmic domain with two conserved motifs.42 They form antiparallel homotypic adhesive complexes with adjacent cells after dimerization and clustering.40,41,44 They are essential proteins for morphogenesis and tissue homeostasis.45 Cadherins regulate the plasticity and control the passage of solutes, water, and lymphoid cells across the cell layer through epithelial and endothelial cell junctions.46 The superfamily of transmembrane cadherin proteins is comprised of more than 100 members in humans, including other classical cadherins, numerous proto-cadherins, and cadherin-related proteins.47 Several tissue-specific cadherins have been identified, including epithelial (E)-cadherin, neuronal (N)-cadherin, placental (P)-cadherin, vascular endothelial (VE)- cadherin, and others.8 Disruption in the expression or function of such individual cadherins results in abnormal development of the respective organs.41
Expression of N-cadherin and β-catenin in human meningioma in correlation with peritumoral edema
Published in International Journal of Neuroscience, 2018
Robert Rutkowski, Robert Chrzanowski, Magdalena Trwoga, Jan Kochanowicz, Grzegorz Turek, Zenon Mariak, Joanna Reszeć
Cadherins are a family of glycoproteins that are associated with cell adhesion mechanisms. In humans, there are more than 80 proteins belonging to the cadherin family, like E- and P-cadherins which are regarded as the epithelial subtype. Cadherins are composed of an extracellular part that mediates calcium-dependent interactions between cadherins and a transmembrane and cytoplasmic part [4]. Many data show that the alterations between the intercellular reactions, the expression and function of cell-cell and cell-matrix proteins expression are associated with progression to the malignancy [5]. E-cadherin is known to be expressed in most of the epithelial neoplasms, including meningiomas. In most of the data concerning low-grade meningiomas, the researchers presented a significant E-cadherin expression. Schwechheimer et al. showed a significant E-cadherin expression in all of the examined meningiomas regardless of the histomorphological subtypes [5,6]. However, E-cadherin expression is lost in many types of the carcinomas, including breast cancer or colorectal cancer [7,8].